rs2289219

Positions:

• chr15-40773692-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000220496.9(DNAJC17):​c.792+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,564,784 control chromosomes in the GnomAD database, including 87,331 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (6288 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81043 hom.)
• Consequence: DNAJC17 ENST00000220496.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

Genes affected

DNAJC17 (HGNC:25556): (DnaJ heat shock protein family (Hsp40) member C17) Predicted to enable RNA binding activity. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II and toxin transport. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC17	NM_018163.3	c.792+35G>A		intron_variant		ENST00000220496.9	NP_060633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC17	ENST00000220496.9	c.792+35G>A		intron_variant		1	NM_018163.3	ENSP00000220496	P1
DNAJC17	ENST00000559238.5	c.*820+35G>A		intron_variant, NMD_transcript_variant		5		ENSP00000453354
DNAJC17	ENST00000561110.5	n.339+35G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38387 AN: 152052 Hom.: 6286 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.290 AC: 66282 AN: 228200 Hom.: 11364 AF XY: 0.306 AC XY: 37969 AN XY: 124010

Gnomad AFR exome AF: 0.0566

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.0698

Gnomad SAS exome AF: 0.354

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.330 AC: 465497 AN: 1412612 Hom.: 81043 Cov.: 22 AF XY: 0.333 AC XY: 233995 AN XY: 703692

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.252 AC: 38391 AN: 152172 Hom.: 6288 Cov.: 32 AF XY: 0.256 AC XY: 19061 AN XY: 74396

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0731

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.248

Alfa AF: 0.324 Hom.: 7839

Bravo AF: 0.221

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2289219; hg19: chr15-41065890; COSMIC: COSV55024917; COSMIC: COSV55024917;